Presynaptic inhibitory effects of the peptides NPY, PYY and PP on nicotinic EPSPs in guinea‐pig gastric myenteric neurones.

Abstract

SUMMARY1. Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) affect gastrointestinal effector systems. Although their precise mode of action is unknown it is suggested that their effects are partly mediated by enteric neurones. Therefore, the aim of this study was to investigate the effects of NPY, PYY, avian PP (aPP) and bovine PP (bPP) on the electrophysiological behaviour of gastric myenteric neurones using intracellular recording methods.2. In all thirty-one neurones tested, electrical stimulation of interganglionic fibre tracts evoked cholinergic, nicotinic fast excitatory postsynaptic potentials (fEPSPs). NPY, PYY and bPP (10-500 nM) inhibited the fEPSPs in a concentrationdependent manner. Additionally, these peptides reversibly abolished spontaneously occurring nicotinic fEPSPs. None of the peptides exhibited any effect on the response to exogeneously applied acetylcholine or on the postsynaptic excitability of the neurones. The inhibitory effects on the fEPSPs could not be reversed by perfusion of the a-adrenoceptor antagonist, phentolamine (1 ,(M).3. In contrast, aPP had no significant effect on fEPSPs even when perfused at the high concentration of 1 ,IM.4. The results suggest that NPY, PYY and bPP, but not aPP, act presynaptically to inhibit acetylcholine release from myenteric neurones of the gastric corpus, thereby suppressing fEPSPs. The study indicates a modulatory role for NPY, PYY and bPP in synaptic interactions within the enteric nervous system.

Subpopulations of Gastric Myenteric Neurons Are Differentially Activated via Distinct Serotonin Receptors: Projection, Neurochemical Coding, and Functional Implications

“…In agreement, nitric oxide evoked a presynaptic reduction of excitatory input to myenteric neurons, although this has been attributed mainly to inhibition of peptidergic synapses (Tamura et al, 1993). In the stomach, it has been shown that neuropeptide Y acted presynaptically to reduce cholinergic fast EPSPs, which would result in reduced release of acetylcholine (Schemann and Tamura, 1991). Because most nitrergic neurons in the stomach were neuropeptide Y-immunoreactive , this peptide might also be involved in the 5-OHI P-induced decrease of the stimulusevoked contractions.…”

Vagal neurocircuitry and its influence on gastric motility

“…As PYY3-36 readily crosses the blood–brain barrier 146 , an effect on neurons of the DMV is probable; in fact, brainstem microinjections of PYY induce either excitation or inhib ition of gastric motility, depending on the basal activity of the stomach 147–151 . Electrophysiological recordings confirm a Y2 receptor-mediated response of PYY on identified vagal motor neurons 84,86 as well as on enteric neurocircuits 152 . The mechanism of action of PYY on vagal motor neurons varied in concert with brainstem levels of cAMP 84 , suggesting a means to explain the puzzling opposing responses (either excitation or inhibition of gastric motility) observed in the in vivo experiments on gastric motility 147,148 .…”

Regional differences in the sympathetic innervation of the Guinea pig large intestine by neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerves of divergent extrinsic origin

“…Because NPY is capable of exerting profound effects, both facilitatory and inhibitory, on ganglionic transmission in enteric neurons (Schemann and Tamura, 1992;Zafirov et al, 1992;Cunningham et al, 1994a,b;Browning et al, 1996;Hirai et al, 1997), the effects of this previously unknown, nonnoradrenergic, sympathetic innervation by NPY-containing nerves on colonic motility and secretion merit investigation.…”